A role for Oncostatin M in the impairment of glucose homeostasis in obesity

CONTEXT: Oncostatin M (OSM) plays a key role in inflammation, but its regulation and function during obesity is not fully understood. OBJECTIVE: The aim of this study was to evaluate the relationship of OSM with the inflammatory state that leads to impaired glucose homeostasis in obesity. We also assessed whether OSM immunoneutralization could revert metabolic disturbances caused by a high-fat diet (HFD) in mice. DESIGN: 28 patients with severe obesity were included and stratified into two groups: (1) glucose levels 100 mg/dL. White adipose tissue was obtained to examine OSM gene expression. Human adipocytes were used to evaluate the effect of OSM in the inflammatory response, and HFD-fed C57BL/6J mice were injected with anti-OSM antibody to evaluate its effects. RESULTS: OSM expression was elevated in subcutaneous and visceral fat from patients with obesity and hyperglycemia, and correlated with Glut4 mRNA levels, serum insulin, homeostatic model assessment of insulin resistance, and inflammatory markers. OSM inhibited adipogenesis and induced inflammation in human adipocytes. Finally, OSM receptor knockout mice had increased Glut4 mRNA levels in adipose tissue, and OSM immunoneutralization resulted in a reduction of glucose levels and Ccl2 expression in adipose tissue from HFD-fed mice. CONCLUSIONS: OSM contributes to the inflammatory state during obesity and may be involved in the development of insulin resistance

Use of infrared thermography to estimate brown fat activation after a cooling protocol in patients with severe obesity that underwent bariatric surgery

Background: In contrast to the energy-storing role of white adipose tissue (WAT), brown adipose tissue (BAT) acts as the main site of non-shivering thermogenesis in mammals and has been reported to play a role in protection against obesity and associated metabolic alterations in rodents. Infrared thermography (IRT) has been proposed as a novel non-invasive, safe, and quick method to estimate BAT thermogenic activation in humans. The aim of this study is to determine whether the IRT could be a potential new tool to estimate BAT thermogenic activation in patients with severe obesity in response to bariatric surgery. Methods: Supraclavicular BAT thermogenic activation was evaluated using IRT in a cohort of 31 patients (50 ± 10 years old, BMI = 44.5 ± 7.8; 15 undergoing laparoscopy sleeve gastrectomy and 16 Roux-en-Y gastric bypass) at baseline and 6 months after a bariatric surgery. Clinical parameters were determined at these same time points. Results: Supraclavicular BAT-related activity was detected in our patients by IRT after a cooling stimulus. The BAT thermogenic activation was higher at 6 months after laparoscopy sleeve gastrectomy (0.06 ± 0.1 vs 0.32 ± 0.1), while patients undergoing to a roux-en-Y gastric bypass did not change their thermogenic response using the same cooling stimulus (0.09 ± 0.1 vs 0.08 ± 0.1). Conclusions: Our study postulates the IRT as a potential tool to evaluate BAT thermogenic activation in patients with obesity before and after a bariatric surgery. Further studies are needed to evaluate differences between LSG technique and RYGB on BAT activation. Keywords: Brown adipose tissue; Infrared thermography; Metabolic surgery; Obesity

White adipose tissue-infiltrated CD11b+ myeloid cells are a source of S100A4, a new potential marker of hepatic damage

Context The endocrine and immunological properties of subcutaneous vs. visceral adipose tissue (sWAT and vWAT, respectively) have turned a milestone in the study of metabolic diseases. The cytokine S100A4 has been reported to be elevated in obesity and to have a role in adipose tissue dysfunction. However, the cellular source in adipose tissue and its potential role in hepatic damage in obesity has not been elucidated. Objective We aim to study the regulation of S100A4 in immune cells present in sWAT and vWAT, as well as its potential role as a circulating marker of hepatic inflammation and steatosis. Design A cohort of 60 patients with obesity and distinct metabolic status was analyzed. CD11b+ myeloid cells and T cells were isolated from sWAT and vWAT by magnetic-activating cell sorting, and RNA was obtained. S100A4 gene expression was measured, and correlation analysis with clinical data was performed. Liver biopsies were obtained from 20 patients, and S100A4 circulating levels were measured to check the link with hepatic inflammation and steatosis. Results S100A4 gene expression was strongly upregulated in sWAT- vs. vWAT-infiltrated CD11b+ cells, but this modulation was not observed in T resident cells. S100A4 mRNA levels from sWAT (and not from vWAT) CD11b+ cells positively correlated with glycemia, triglycerides and TNF-α gene expression. Finally, circulating S100A4 directly correlated with liver steatosis and hepatic inflammatory markers. Conclusion Our data suggest that sWAT-infiltrated CD11b+ cells could be a major source of S100A4 in obesity. Moreover, our correlations identify circulating S100A4 as a potential novel biomarker of hepatic damage and steatosis